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Discovery of (5-Phenylfuran-2-yl)methanamine Derivatives as New Human Sirtuin 2 Inhibitors.
- Source :
- Molecules; Aug2019, Vol. 24 Issue 15, p2724-2724, 1p, 1 Color Photograph, 5 Diagrams, 3 Charts, 1 Graph
- Publication Year :
- 2019
-
Abstract
- Human sirtuin 2 (SIRT2), a member of the sirtuin family, has been considered as a promising drug target in cancer, neurodegenerative diseases, type II diabetes, and bacterial infections. Thus, SIRT2 inhibitors have been involved in effective treatment strategies for related diseases. Using previously established fluorescence-based assays for SIRT2 activity tests, the authors screened their in-house database and identified a compound, 4-(5-((3-(quinolin-5-yl)ureido)methyl)furan-2-yl)benzoic acid (20), which displayed 63 ± 5% and 35 ± 3% inhibition against SIRT2 at 100 μM and 10 μM, respectively. The structure-activity relationship (SAR) analyses of a series of synthesized (5-phenylfuran-2-yl)methanamine derivatives led to the identification of a potent compound 25 with an IC<subscript>50</subscript> value of 2.47 μM, which is more potent than AGK2 (IC<subscript>50</subscript> = 17.75 μM). Meanwhile, 25 likely possesses better water solubility (cLogP = 1.63 and cLogS = −3.63). Finally, the molecular docking analyses indicated that 25 fitted well with the induced hydrophobic pocket of SIRT2. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 24
- Issue :
- 15
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 138015031
- Full Text :
- https://doi.org/10.3390/molecules24152724